Protoporphyrin-IX accumulation and cutaneous tumor regression in mice using a ferrochelatase inhibitor
Protoporphyrin-IX accumulation and cutaneous tumor regression in mice using a ferrochelatase inhibitor
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DOI：
10.1016/s0304-3835(02)00284-7
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发表时间：
2002-12-10
期刊：
影响因子：
9.7
通讯作者：
Athar, M
中科院分区：
文献类型：
--
作者：
Bhasin, G;Kausar, H;Athar, M
在癌症的光动力疗法(PDT)中，使用内源性的卟啉替代光敏剂注射是一个快速发展的研究领域。通过抑制半生物合成原位积累原卟啉-IX(PpIX)是一种新的肿瘤细胞光动力治疗方法。用铅(一种已知有效的铁络合酶抑制剂)研究了PPIX在小鼠体内蓄积和皮肤肿瘤消退的动力学。皮肤肿瘤暴露于不同剂量的铁络合酶抑制剂(铅)和不同持续时间和剂量的可见光。在1个月内第二次注射铅后48h，PpIX水平(血液、皮肤和肿瘤)升高幅度最大。在648J/cm(2)的可见光照射下(每次照射间隔10分钟，每次照射15分钟，每次照射1小时)的小鼠肿瘤消退率最高。连续治疗6天后，大部分动物肿瘤几乎完全消退。光照后肿瘤组织病理切片可见坏死组织，淋巴细胞、单核细胞和中性粒细胞变性。由于本研究中使用的铁络合酶抑制剂(铅)是有毒的，因此必须继续寻找一种安全、无毒的抑制剂来增强增敏剂介导的PDT。(C)2002爱思唯尔科学爱尔兰有限公司。保留所有权利。
The use of endogenously created porphyrins as an alternative to photosensitizer injection for photodynamic therapy (PDT) of cancer is a rapidly evolving area of study. In-situ accumulation of protoporphyrin-IX (PpIX) by hemebiosynthesis inhibition represents a novel method for PDT of cancer cells. The kinetics of PpIX accumulation and cutaneous tumor regression in mice was studied using lead (a known and effective inhibitor of ferrochelatase). Cutaneous tumors were exposed to various doses of ferrochelatase enzyme inhibitor (lead) and to different durations and doses of visible light. The maximum increase in PpIX levels (blood, skin and tumor) was observed 48 h after the parenteral administration of second injection of lead within a period of 1 month. The maximum tumor regression was observed in mice that were exposed to visible light at a light dose of 648 J/cm(2) (1 h exposure in four sessions of 15 min, with a gap of 10 min between each exposure). Continuous treatment for 6 consecutive days resulted in almost complete regression of the tumors in most of the animals. Histopathological sections of tumors after light exposure showed necrotic tissue with degenerated lymphocytes, monocytes, and neutrophils. Since the ferrochelatase inhibitor (lead) used in the present study is toxic, the search must continue for a safe, non-toxic inhibitor to enhance sensitizer-mediated PDT. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.